You are focusing on the potential of inhibiting calpains, enzymes which breaks down proteins, and using calpain inhibitors in spinal cord injury treatment. What improvements do you except if you manage to inhibit cell death by calpain inhibition?
The neurodegeneration following spinal cord injury is complex and involves multiple mechanisms, one of which is excessive calpain activation. Calpain inhibition alone in animal models has significant but modest effects in reducing tissue damage and improving functional recovery. It can mean the different between weight-supported and non-weight-supported stepping. Targeting multiple mechanisms will be necessary to achieve robust neuroprotection following spinal cord injury.

What promising results have you reached so far?
The most promising results we’ve so far are about the knockdown of calpain I in rats. We reduced the expression of the gene for calpain I through gene therapy. That gives a more robust improvement in functional recovery compared with currently available drugs which are not very specific. These results are being prepared for publication and will be presented at the Society for Neuroscience meeting in San Diego, 13-17th of November.

What projects do you think are the most promising when it comes to bringing patients paralysed by spinal cord injuries closer to a cure?
This depends on what is defined as a cure. There have been tremendous advances in physical therapy for individuals with incomplete spinal cord injury to facilitate walking. Currently available bioengineering can enable a paralyzed individual to stand, a quadriplegic to grasp, and can provide improved bowel and bladder control. These are a cure, at least in some respects, but are far from ideal. Restoring the normal spinal cord circuitry is the long term goal.

Concerning the current available bioengineering you mentioned, Rex Bionics’ exoskeleton can enable a person to stand, walk and climb the stairs. What are the implications of this new kind of complement to the wheelchair?
An example of the engineering approach is that a spinal cord-injured faculty colleague received an early version of electrode implants into the four major muscle groups involved in standing. Rex Bionics’ system doesn’t involve the implanting of electrodes. These electrodes go to a radio coil just underneath the skin in the abdomen. He uses an external battery pack device over that coil. By pressing a button electrical signals will be sent to those electrodes causing the muscles to contract and allows him to stand. For example, at a grocery store he can stand and reach something on a higher shelf. One person who has those implants is an auto mechanic who can stand and work on cars. At home someone can get something out from an upper cupboard. One person said it allowed him to stand and kiss his wife for the first time in years. It doesn’t provide ankle support like when we stand; they have to wear ankle boots. They don’t have the coordination and it doesn’t allow direct walking. But it allows another level of freedom that that they didn’t have before. Even that limited movement can be very enabling for an individual with a spinal cord injury. The engineering is currently, at least, ahead of the biomedical approaches.

What are the biggest challenges on the way to fully restored function after spinal cord injuries?
The challenges are several—to minimize the damage that occurs following injury, regrow damaged neurons and connect them to their proper target, and also promote remyelination. While we are getting closer and advances are being made in each of these areas, a complete cure remains in the distant future.

* Photo courtesy of University of Kentucky